Pre-clinical characterization of CTC-96 in a non-spermicidal topical virucide

Abstract

The small organo-cobalt complex, CTC-96 (Doxovir™), is under development for prophylactic use in a topical vaginal microbicide. Such an anti-STD microbicide should be effective against a range of microbes, especially viruses, but harmless to the host, to her natural microbial flora and to her reproductive potential. The suitability of CTC-96 is supported by findings on its toxicology and anti-viral effects summarized here. CTC-96 is active against herpes simplex virus (HSV), human immunodeficiency virus (HIV), and human papillomavirus (HPV), which are the causative agents of genital herpes, AIDS, and anogenital warts, respectively, and there are preliminary indications of CTC-96 activity against other STD pathogens, too. Documentation of anti-HIV activity has been extended from laboratory strains to clinical isolates. We also report that CTC-96 is very weakly spermicidal in the Sanders-Cramer assay, and is not genotoxic either in the Ames mutagenesis test (with metabolic activation) or in the mouse clastogenesis (micronucleus) test. Toxicity is seen in mice injected (i.p.) with 80mg/kg body weight, but not with 40mg/kg. Obtaining this lower concentration in humans would require complete adsorption of 100 times the CTC-96 present in the most concentrated anticipated microbicide formulation. 0.1% CTC-96 has proven completely effective against infection by HSV in mouse and guinea pig models, and HIV or HPV in cultured cell or human tissue explant models, respectively. Experiments are now underway to better characterize CTC-96 potency against clinical HIV isolates, against infection by fusion with infected cells, and to evaluate CTC-96 for treatment of HPV infected human tissue explants in SCID mice. A preliminary human safety trial of CTC-96 has been conducted in eyes for indications of ocular herpes and inflammation. CTC-96 showed no ill effects when an eye drop containing 50μg/ml CTC-96 was given to healthy volunteers. This, together with animal and in vitro evidence, suggests that a CTC-96 based microbicide can be both innocuous and effective.